title: Antimicrobial activity of a chimeric enzybiotic towards Staphylococcus aureus.
abstract: Phage lytic enzymes (enzybiotics) have gained attention as prospective tools to eradicate Gram-positive pathogens resistant to antibiotics. Attempts to purify the P16 endolysin of Staphylococcus aureus phage P68 were unsuccessful owing to the poor solubility of the protein. To overcome this limitation, we constructed a chimeric endolysin (P16-17) comprised of the inferred N-terminal d-alanyl-glycyl endopeptidase domain and the C-terminal cell wall targeting domain of the S. aureus phage P16 endolysin and the P17 minor coat protein, respectively. The domain swapping approach and the applied purification procedure resulted in soluble P16-17 protein, which exhibited antimicrobial activity towards S. aureus. In addition, P16-17 augmented the antimicrobial efficacy of the antibiotic gentamicin. This synergistic effect could be useful to reduce the effective dose of aminoglycoside antibiotics.
authors.affiliation: Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
authors.forename: Salim
authors.initials: S
authors.lastname: Manoharadas
authors.forename: Angela
authors.initials: A
authors.lastname: Witte
authors.forename: Udo
authors.initials: U
authors.lastname: Bläsi
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D001435:Bacteriophages / Q000201:enzymology* / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005839:Gentamicins / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D036022:Capsid Proteins; D005839:Gentamicins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D010450:Endopeptidases